POS1040 SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR: AS ASSESSED BY LABORATORY PARAMETERS – RESULTS FROM A PHASE 2 TRIAL IN PSORIATIC ARTHRITIS AND 2 PHASE 3 TRIALS IN PSORIASIS
Authors: R. M. Fleischmann, D. Thaçi, M. Gooderham, B. Strober, N. J. Korman, S. Banerjee, T. Lehman, M. Nowak, A. Sreih, A. Morita, P. J. Mease
Journal: Annals of the Rheumatic Diseases (2022)

Background Deucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA, 1 and vs PBO or apremilast in 2 Phase 3 PsO trials. 2 Objectives To assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials. Methods The Phase 2 double-blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double-blind PsO trials, POETYK PSO-1 and POETYK PSO-2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed. Results In the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC-, PBO-, and apremilast-treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms. Table 1. Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16 PsA Phase 2 PsO Phase 3 a CTCAE Term Grade Placebo (n=66 ) n (% ) DEUC 6 mg QD (n=70 ) n (% ) DEUC 12 mg QD (n=67 ) n (% ) Placebo (n=419 ) n (% ) DEUC 6 mg QD (n=842 ) n (% ) Apremilast 30 mg BID (n=422 ) n (% ) BL Wk 1-16 BL Wk 1-16 BL Wk 1-16 BL Wk 1-16 BL Wk 1-16 BL Wk 1-16 Lymphocyte count decreased 34 00 00 00 1 (1.4)0 00 00 00 1 (0.2)0 00 1 (0.1)0 00 00 Neutrophil count decreased 34 00 00 00 00 00 00 00 1 (0.2)0 1 (0.1) 0 1 (0.1)0 00 00 Platelet count decreased 34 00 00 00 00 00 00 00 00 00 00 00 00 Anaemia 34 0N/A 0N/A 0N/A 0N/A 0N/A 0 N/A 0N/A 0N/A 0N/A 0 N/A 0N/A 1 (0.2) N/A Alanine aminotransferase increased 34 00 0 0 00 00 0 0 00 0 0 00 00 00 00 0 0 Aspartate aminotransferase increased 34 00 00 00 00 0 0 1 (1.6)0 00 0 0 0 0 1 (0.1)0 00 1 (0.2) 0 CPK increased 34 00 1 (1.5) 0 00 0 0 00 01 (1.6) 1 (0.2) 0 3 (0.7) 1 (0.2) 1 (0.1) 0 5 (0.6) 6 (0.7) 1 (0.2)0 2 (0.5) 1 (0.2) Cholesterol high 34 00 00 00 00 00 0 0 0 0 0 0 0 0 0 0 00 00 Hypertriglyceridemia 34 00 0 0 1 (1.4) 1 (1.4) 2 (2.9) 1 (1.4) 1 (1.6) 0 4 (6.0) 0 2 (0.5) 1 (0.2) 6 (1.5) 0 4 (0.5)1 (0.1) 12 (1.5)2 (0.2) 3 (0.7) 0 8 (2.0) 0 a POETYK PSO-1 and PSO-2 pooled data. BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week. Conclusion DEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two-thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO. References [1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis . (In Press). [2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021. Acknowledgements This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb. Disclosure of Interests Roy M. Fleischmann Consultant of: Abbvie, Acea, Akros, Amgen, Bristol Myers Squibb, Celtrion, Eli Lilly &amp; Co., Galvani, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi Aventis, Taiho, and UCB., Grant/research support from: AbbVie, Acea, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly &amp; Co., Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Pfizer, Roche/Genentech, Samumed, Sanofi Aventis, and UCB, Diamant Thaçi Consultant of: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Melinda Gooderham Consultant of: Investigator, speaker, advisory board member or consultant for: AbbVie, Akros, Amgen, Anaptys Bio, Arcutis, Aslan, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, SUN Pharma, and UCB., Bruce Strober Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi-Genzyme; Scientific co-director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis., Neil J Korman Consultant of: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi-Genzyme., Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Employees and shareholders of Bristol Myers Squibb, Employee of: Employees and shareholders of Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Akimichi Morita Consultant of: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Grant/research support from: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB;